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Diabetes Publish Ahead of Print published online ahead of print February 7, 2007
DOI: 10.2337/db06-1445
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Original Research

Characterization of donor dendritic cells and enhancement of dc efflux with cc-chemokine ligand 21: a novel strategy to prolong islet allograft survival

Paolo Fiorina1,,3, Mollie Jurewicz1, Tanaka Katsunori1, Negin Behazin1, Andrea Augello1, Andrea Vergani1,,3, Uli Von Adrian4, Neal R. Smith2, Mohamed H. Sayegh1, and Reza Abdi1

1Transplantation Research Center (TRC), Children's Hospital and Brigham and Women's Hospital, Harvard Medical School, Boston, USA
2Pathology, Massachusetts General Hospital, Harvard Medical School, Boston
3Medicine, San Raffaele Scientific Institute, Milan, Italy
4CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, USA

Correspondence: rabdi{at}rics.bwh.harvard.edu

Dendritic cells (DC) are the most potent antigen-presenting cells, yet little data are available on the differential characteristics of donor and recipient DC (dDC and rDC) during the process of islet allograft rejection. DTR-GFP-DC mice provide a novel tool to monitor DC trafficking and characteristics during allograft rejection. We show rapid migration of dDC to recipient lymphoid tissues as early as 3 hours post islet allo-transplantation. Compared with rDC, dDC express different patterns of chemokine receptors, display differential proliferative capacity, and exhibit a higher level of maturity; these findings could be attributed to the effects of injury that dDC undergo during islet cell preparation and engraftment. Intriguingly, we detected dDC in the spleen of recipients long after rejection of islet allografts. Given that dDC express high levels of CCR7, islets were cultured before transplant with the ligand for CCR7 (CCL21). This novel method, which enabled us to enhance the efflux of dDC from islet preparations, resulted in a prolongation of islet allograft survival in immunocompetent recipients. This study introduces dDC and rDC as two distinct types of DC and provides novel data with clinical implications to use chemokine-based DC-depleting strategies to prolong islet allograft survival.

Key-word: Dendritic cells, islet transplantation, chemokines.


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Copyright © 2007 by the American Diabetes Association.